Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cognitive dysfunction. ME/CFS patients often report a prodrome consistent with infection. We present a multi-omics analysis based on plasma metabolomic and proteomic profiling, and immune responses to microbial stimulation, before and after exercise.

Metabolome informs about the chemical exposome and links to brain health.

The metabolome is an intermediate phenotype, summarizing the profile of all small molecules (<1.5 kDa) in biospecimens. The metabolome provides a readout for the net influence of the chemical exposome, diet, gut microbiome, and genome on human health.

A standardized nontargeted metabolomics method for cross-laboratory comparison of food profiles.

Food composition has been traditionally defined by 35-160 chemical components with established nutritional significance for human health. Modern omics technologies have revealed that the chemical complexity of food is far greater, offering the potential to deepen our understanding of food composition to more precisely inform data-driven solutions across food systems. However, challenges in generating comparable omics data have limited the utility of omics technologies at the scale required to expand food composition databases.

Heightened innate immunity may trigger chronic inflammation, fatigue and post-exertional malaise in ME/CFS.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue, post-exertional malaise (PEM), and cognitive dysfunction. ME/CFS patients often report a prodrome consistent with infection. We present a multi-omics analysis based on plasma metabolomic and proteomic profiling, and immune responses to microbial stimulation, before and after exercise.

Heat-induced phosphatidylserine changes drive HSPA1A's plasma membrane localization.

HSPA1A is a molecular chaperone crucial in cell survival. In addition to its cytosolic functions, HSPA1A translocates to heat-shocked and cancer cells' plasma membrane (PM). In cancer, PM-localized HSPA1A (mHSPA1A) is associated with increased tumor aggressiveness and therapeutic resistance, suggesting that preventing its membrane localization could have therapeutic value.

The Dietary Biomarkers Development Consortium: An Initiative for Discovery and Validation of Dietary Biomarkers for Precision Nutrition.

Unlabelled: Diet is a complex exposure that affects health across the lifespan. Objective biomarkers that can reliably reflect intake of nutrients, foods, and dietary patterns with sufficient accuracy are an important tool for assessing associations of diet with health outcomes. Advances in metabolomics, coupled with feeding trials and high-dimensional bioinformatics analyses, pave the way for discovering compounds that can serve as sensitive and specific biomarkers of dietary exposures.

A substrate-multiplexed platform for profiling enzymatic potential of plant family 1 glycosyltransferases.

Plants have expanded various biosynthetic enzyme families to produce a wide diversity of natural products; however, most enzymes encoded in plant genomes remain uncharacterized, highlighting the need for new functional genomic approaches. Here, we report a platform enabling the rapid functional characterization of plant family 1 glycosyltransferases, which serve important roles in plant development, defense, and communication. Using substrate-multiplexed reactions, mass spectrometry, and automated analysis, we screen 85 enzymes against a diverse library of 453 natural products, for a total of nearly 40,000 possible reactions.

The effect of parenteral vitamin B treatment on its plasma metabolomic profile and on functional biomarkers of its deficiency.

Diagnosis of vitamin B (B) deficiency is hampered by the low specificity cut-offs of blood-based biomarkers, like serum B and holo-transcobalamin (HoloTc), or B-associated metabolites like methylmalonic acid (MMA) and homocysteine (Hcy) concentrations, or their combinations computed as combined B (cB). We assessed B deficiency through non-invasive [C]-propionate oxidation breath test to derive functional cut-off and tested its sensitivity in response to acute change in B status in low B adult male participants by parenterally administering 3 mg hydroxocobalamin and profiling through untargeted and targeted B related metabolites. The functional deficiency cut-off, based on a breakpoint analysis of [C]-propionate oxidation with B concentrations, was 144 pmol/L [95% CI 106.

MassCube improves accuracy for metabolomics data processing from raw files to phenotype classifiers.

Nontargeted peak detection in LC-MS-based metabolomics must become robust and benchmarked. We present MassCube, a Python-based open-source framework for MS data processing that we systematically benchmark against other algorithms and different types of input data. From raw data, peaks are detected by constructing mass traces through signal clustering and Gaussian-filter assisted edge detection.

Circadian ontogenetic metabolomics atlas: an interactive resource with insights from rat plasma, tissues, and feces.

Circadian rhythms regulate key physiological processes through clock genes in central and peripheral tissues. While circadian gene expression during development has been well studied, the temporal dynamics of metabolism across tissues remain less understood. Here, we present the Circadian Ontogenetic Metabolomics Atlas (COMA), which maps circadian metabolic rhythms across 16 rat anatomical structures.

Discrimination of Normal from Slow-Aging Mice by Plasma Metabolomic and Proteomic Features.

Tests that can predict whether a drug is likely to extend mouse lifespan could speed up the search for anti-aging drugs. We have applied a machine learning algorithm, XGBoost regression, to seek sets of plasma metabolites that can discriminate control mice from mice treated with an anti-aging diet (caloric restriction) or any of four anti-aging drugs. When the model is trained on any four of these five interventions, it predicts significantly higher lifespan extension in mice exposed to the intervention which was not included in the training set.

A universal language for finding mass spectrometry data patterns.

Despite being information rich, the vast majority of untargeted mass spectrometry data are underutilized; most analytes are not used for downstream interpretation or reanalysis after publication. The inability to dive into these rich raw mass spectrometry datasets is due to the limited flexibility and scalability of existing software tools. Here we introduce a new language, the Mass Spectrometry Query Language (MassQL), and an accompanying software ecosystem that addresses these issues by enabling the community to directly query mass spectrometry data with an expressive set of user-defined mass spectrometry patterns.

Longitudinal Lipidomic Profile of Subclinical Peripheral Artery Disease in American Indians: The Strong Heart Family Study.

Introduction: Peripheral artery disease (PAD) and dyslipidemia are both independent predictors of cardiovascular disease, but the association between individual lipid species and subclinical PAD, assessed by ankle-brachial index (ABI), is lacking in large-scale longitudinal studies.

Methods: We used liquid chromatography-mass spectrometry to repeatedly measure 1,542 lipid species from 1,886 American Indian adults attending 2 clinical examinations (mean ~5 years apart) in the Strong Heart Family Study. We used generalized estimating equation models to identify baseline lipid species associated with change in ABI and the Cox frailty regression to examine whether lipids associated with change in ABI were also associated with incident coronary heart disease (CHD).

genotype and biological age impact inter-omic associations related to bioenergetics.

Apolipoprotein E () modifies human aging; specifically, the ε2 and ε4 alleles are among the strongest genetic predictors of longevity and Alzheimer's disease (AD) risk, respectively. However, detailed mechanisms for their influence on aging remain unclear. In the present study, we analyzed multi-omic association patterns across genotypes, sex, and biological age (BA) axes in 2,229 community dwelling individuals.

Circulating lipidome underpins gender differences in the pathogenesis of type 2 diabetes.

Metabolic alterations in human lipidome significantly impact various chronic diseases including type 2 diabetes (T2D). However, epidemiology and clinical studies have yet to identify clinically meaningful lipid markers for T2D. Fatty acids (FAs) are the backbone of lipid species.

Lipidomic Markers of Processed Meat and Unprocessed Red Meat Intake and Risk of Diabetes in American Indians.

Objective: To identify lipidomic markers of habitual unprocessed red meat and processed meat intake and evaluate their associations with diabetes risk in American Indians.

Research Design And Methods: We studied 1,816 participants from the Strong Heart Family Study. Using untargeted liquid chromatography-mass spectrometry, we quantified 1,542 lipids (518 known) in fasting plasma at baseline and follow-up (∼5 years apart).

Dynamic Lipidome Reorganization in Response to Heat Shock Stress.

The heat shock response (HSR) is a conserved cellular mechanism critical for adaptation to environmental and physiological stressors, with broad implications for cell survival, immune responses, and cancer biology. While the HSR has been extensively studied at the proteomic and transcriptomic levels, the role of lipid metabolism and membrane reorganization remains underexplored. Here, we integrate mass spectrometry-based lipidomics with RNA sequencing to characterize global lipidomic and transcriptomic changes in HeLa cells exposed to three conditions: control, heat shock (HS), and HS with eight hours of recovery.

Denoising Search doubles the number of metabolite and exposome annotations in human plasma using an Orbitrap Astral mass spectrometer.

Chemical exposures may affect human metabolism and contribute to the etiology of neurodegenerative disorders such as Alzheimer's disease. Identifying these small metabolites involves matching experimental spectra to reference spectra in databases. However, environmental chemicals or physiologically active metabolites are usually present at low concentrations in human specimens.

Resolving multi-image spatial lipidomic responses to inhaled toxicants by machine learning.

Regional responses to inhaled toxicants are essential to understand the pathogenesis of lung disease under exposure to air pollution. We evaluate the effect of combined allergen sensitization and ozone exposure on eliciting spatial differences in lipid distribution in the mouse lung that may contribute to ozone-induced exacerbations in asthma. We demonstrate the ability to normalize and segment high resolution mass spectrometry imaging data by applying established machine learning algorithms.

Analyses of Saliva Metabolome Reveal Patterns of Metabolites That Differentiate SARS-CoV-2 Infection and COVID-19 Disease Severity.

Background: The metabolome of COVID-19 patients has been studied sparsely, with most research focusing on a limited number of plasma metabolites or small cohorts. This is the first study to test saliva metabolites in COVID-19 patients in a comprehensive way, revealing patterns significantly linked to disease and severity, highlighting saliva's potential as a non-invasive tool for pathogenesis or diagnostic studies.

Methods: We included 30 asymptomatic subjects with no prior COVID-19 infection or vaccination, 102 patients with mild SARS-CoV-2 infection, and 61 hospitalized patients with confirmed SARS-CoV-2 status.

Drug-Based Lifespan Extension in Mice Strongly Affects Lipids Across Six Organs.

Caloric restriction is associated with slow aging in model organisms. Additionally, some drugs have also been shown to slow aging in rodents. To better understand metabolic mechanisms that are involved in increased lifespan, we analyzed metabolomic differences in six organs of 12-month-old mice using five interventions leading to extended longevity, specifically caloric restriction, 17-α estradiol, and caloric restriction mimetics rapamycin, canagliflozin, and acarbose.

Heat Shock-Induced PI(4)P Increase Drives HSPA1A Translocation to the Plasma Membrane in Cancer and Stressed Cells through PI4KIII Alpha Activation.

HSPA1A, a major heat shock protein, is known to translocate to the plasma membrane (PM) in response to cellular stress and cancer, where it plays protective roles in membrane integrity and stress resistance. Although phosphatidylinositol 4-phosphate [PI(4)P] is essential in this translocation, the signals that trigger and facilitate HSPA1A's movement remain undefined. Given that membrane lipid composition dynamically shifts during stress, we hypothesized that heat shock-induced PI(4)P changes are crucial for HSPA1A's PM localization.

Dynamic Lipidome Reorganization in Response to Heat Shock Stress.

The heat shock response (HSR) is a conserved cellular mechanism critical for adaptation to environmental and physiological stressors, with broad implications for cell survival, immune responses, and cancer biology. While the HSR has been extensively studied at the proteomic and transcriptomic levels, the role of lipid metabolism and membrane reorganization remains underexplored. Here, we integrate mass spectrometry-based lipidomics with RNA sequencing to characterize global lipidomic and transcriptomic changes in HeLa cells exposed to three conditions: control, heat shock (HS), and HS with eight hours of recovery.